Figure 5

BCR/ABL1 resides at 22q11.2 as a result of a cryptic three-way rearrangement between chromosomes 9, 22 and 16 in patient no 6. (a) BCR/ABL1 D-FISH probe (Vysis) showing 1 fusion signal at der(22), 2 red signals at 9 and der(9), 1 green signal at 22 and 1 unexpected green signal at der(16). (b) Chromosome painting confirming the presence of a t(9;22;16)(q34;q11;q?13) in an apparently normal G banding karyotype. (c) FISH with co-hybridization of RP11-326L24 and RP11-643E14 locating RP11-643E14 at the masked Ph while RP11-326L24 is retained at the der(9). (d) A representative metaphase cell with co-hybridization of FISH probes RP11-81P5 and RP11-153P4 identifying RP11-81P5 at the masked Ph. The distal breakpoint of the 9q34 insert is therefore flanked by the BAC clones RP11-81P5 and RP11-326L24. (e) A representative metaphase cell with co-hybridization of FISH probes RP11-92B21 and RP11-223O10 showing RP11-223O10 at normal 22 and der(16), thus confirming the relocation of sequences distal to BCR breakpoint at chromosome 16. (f) Schematic representation of the three-way rearrangement with chromosomes 9 in red, 16 in yellow and 22 in green; note that the der(22) contains material from all three parties. The presence of 9q34.1 sequences embedded within the masked Ph suggests that the t(9;22;16) could be a result of a two stage event: firstly ins(22;9) followed by translocation between der(22)ins(9;22) and 16q.